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Background: Nance-Horan syndrome (NHS) is a rare, frequently underdiagnosed, X-linked disease caused by mutations in the NHS gene. In males, it causes bilateral dense pediatric cataracts, dental anomalies, and facial dysmorphisms. Females traditionally have a more subtle phenotype with discrete lens opacities as an isolated feature. The objective of this case report is to describe a novel variant in NHS, as well as to discuss genotype-phenotype correlations., Methods: Whole-exome sequencing was performed in 3 affected individuals (2 males and 1 female) with pediatric cataracts from the same family, as well as in 2 unaffected members from the same family. Ophthalmological and clinical genetic evaluations were conducted., Results: The likely pathogenic variant c.3333del (p.Phe1111Leufs*9) was found in all affected individuals, as well as in one unaffected female family member. Our family was initially diagnosed with isolated hereditary cataracts, but only after the sequencing results was the phenotype revealed, with the systemic features being identified., Conclusions: This reinforces the importance of genetic testing of bilateral familial pediatric cataracts, especially since systemic features such as dental anomalies and intellectual disability may take years before they develop. Not only did genetic testing help to identify extraocular features, but it also made possible accurate family counseling essential in all pediatric cataract cases.

Molossus molossus is a widely distributed neotropical bat species in the Americas, often found in urban areas. This study evaluated climate change effects on the potential geographic distribution of M. molossus, a natural host of zoonotic pathogens such as Orthohantavirus, in the Neotropical region. Using ecological niche modeling (ENM), models were generated for current (1970-2000) and future (2070) climate scenarios based on two Shared Socioeconomic Pathways (SSP2-4.5 and SSP5-8.5) and two Global Circulation Models (MPI-ESM1-2-LR and IPSL-CM6A-LR). Results indicated that in the current scenario, warm and coastal areas of the Neotropics are suitable for M. molossus occurrence. Risk areas for Orthohantavirus transmission were mapped by overlapping the probability of urban expansion with projections of climatic suitability for the bat. For both future scenarios (2070), projections indicate an expansion of suitable climatic areas for M. molossus over urban expansion zones, specifically in Brazil, Paraguay, Peru, Ecuador, Costa Rica, Honduras, El Salvador, Guatemala, Belize, Mexico, the United States, Cuba, Haiti, the Dominican Republic, and Puerto Rico. However, projections also indicate the Lesser Antilles under climate threat, considering that no climatic suitability areas will remain. These findings provide important information for planning surveillance and mitigation actions for zoonotic risks associated with M. molossus, considering climate change impacts on its geographic distribution in the Neotropical region., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fernando da Silva Moreira reports financial support was provided by Coordination of Higher Education Personnel Improvement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

We investigated the interplay of cardiovascular autonomic and inflammatory profiles in persons with extreme longevity (PEL), their direct offsprings (DO), and a group of controls matched for age and sex with the DO. Cardiac autonomic control was assessed through the heart rate variability (HRV) using spectral and symbolic analysis. The plasma concentration and gene expression of interleukin (IL)-10, IL-6, and TNF-α were quantified. In PEL, the sympatho-vagal is shifted to a vagal predominance and both pro- and anti-inflammatory circulation cytokines are increased compared to DO and controls. Also, no differences were found in HRV between DO and controls. These preliminary results suggest that environmental factors, at least in our small sample, may overcome the impact of heritability on cardiac autonomic control and inflammatory circulation cytokines., Competing Interests: Declarations. Conflict of interest: Nothing to declare. Human and animal rights: The present study involving human participants were reviewed and approved by the Comitato Etico Milano Area 2. Informed consent: All participants provided written informed consent prior to their inclusion in the study. Data availability: Data are available upon reasonable request., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Systematic reviews support the benefits of inspiratory muscle training (IMT) for exercise performance. Recently, many health benefits from IMT have been reported in older adults. Therefore, this work reviewed the literature focusing on IMT effects beyond physical performance in older adults, such as cardiorespiratory, metabolic, and postural balance outcomes. Searches were conducted with the following terms: ("respiratory muscle training" OR "inspiratory muscle training") OR ("inspiratory muscle strength training") AND ("elderly" OR "older" OR "aging" OR "aging"), and using the databases: MEDLINE (PubMed), SCOPUS and EUROPE PMC. Of the 356 articles found, 13 matched the inclusion criteria after screening. Based on reviewed studies, four to eight weeks of IMT (Mostly from 50 % up to 75 % of MIP, 7 days/week) improve cardiac autonomic control at rest and post-exercise, cerebrovascular response to orthostatic stress, static and dynamic balance, blood pressure control, endothelial function, and oxidative stress in older adults. The benefits of IMT in cardiac autonomic and vascular functions are reversed after training cessation. It thus appears that IMT promotes broad physiological gains for the older population. It is necessary to carry out more randomized clinical trials on the subject to confirm the findings of this research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Systematic reviews and meta-analyses support the benefits of inspiratory muscle training (IMT) for sports and clinical populations. A typical application of "standalone" IMT intervention consists of breathing against an inspiratory load (IRL), twice daily, for 5-7 days/wk, for 4-12 wk. However, the application of IRL during aerobic exercise is often seen in a training routine of sports and rehabilitation centers with no evidence-based guide. In this Perspective, we will revisit putative mechanisms underlying the established benefits of "standalone" IMT to support our contention that IMT need not and should not be used during aerobic exercise.

We evaluated the impact of burnt carcasses on the probability of finding Chrysomya albiceps (Wiedemann, 1819) and Lucilia ochricornis (Wiedemann, 1830) (Diptera: Calliphoridae), and the time it took for them to arrive at the experimental carcasss. These species are biological indicators of the postmortem interval (PMI) in forensic scenarios. Using stillborn pig carcasses, this study analysed how different degrees of burning affect the level of attraction and colonisation by these species. Experimental models were subjected to level 2 (CG2) and 4 (CG4) burning according to the Crow-Glassman (CG) scale, ranging from fresh to skeletonization. Generalised Linear Models (GLM) with a Binomial distribution were used to evaluate the influence of decomposition time and experimental treatment on the probability of occurrence of each species. Additionally, survival analyses with the Weibull distribution were used to investigate how long it takes until the arrival of the first fly species in each experimental group. The results indicate that burning affects the probability of occurrence and colonisation time of the studied fly species. Although both species were affected by high degrees of burning, Lucilia ochricornis was more heavily affected than Chrysomya albiceps. This pattern was reflected in the time it took for the first occurrence of each fly species. In both cases, it took longer for flies to arrive at carcasses that had been more severely burnt. In the case of C. albiceps, the longest mean time until a fly was detected (Weibull, α = 79.9 h) happened in the CG4 group, followed by the CG2 group (α = 65.6 h) and the control group (α = 51.5 h). In contrast, for L. ochricornis, the longest mean first occurrence time (α = 85.4 h) was in CG2 group, followed by the Control (α = 49.1 h) and CG4 (α = 54.4 h) groups. This study emphasises the importance of considering whether or not a carcass was burnt and its degree of burning in forensic investigations, given that this variable can influence the accuracy of PMI estimation in crime scenes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to characterize retinitis pigmentosa associated with the eyes shut homolog gene, which causes hereditary retinal degeneration., Methods: The anatomical and functional findings of retinitis pigmentosa in patients with variants of the eyes shut homolog gene were characterized and compared using multimodal imaging and genetic analysis of the variants. Clinical data such as visual acuity, lens status, and refraction were obtained from medical records. Patients underwent an ophthalmic examination, including static visual field, microperimetry, optical coherence tomography, fundus autofluorescence, and fundus photography., Results: Twenty-two patients were included in the study. Several anatomical and functional characteristics of retinitis pigmentosa-eyes shut homolog were identified, including the presence of cataracts, cystoid macular edema, epiretinal membrane, and a tubular visual field. Genetic results revealed 26 distinct variants in the cohort, with 7 novel variants not previously documented or reported in the scientific literature or databases., Conclusion: The findings demonstrate that eyes shut homolog-retinitis pigmentosa manifests in specific patterns, starting in adolescence with mild progression and advancing with age. The integration of multimodal imaging and genetic analysis has provided a detailed understanding of the anatomical and functional features of retinitis pigmentosa-eyes shut homolog. Seven novel variants of the eyes shut homolog gene have been identified. These findings enhance the understanding of eyes shut homolog-related retinitis pigmentosa characteristics of by detailing the spectrum of mutations in this gene within the Brazilian population.

Purpose: We tested the hypothesis that heat stress influences the closed-loop cardio-postural control by an increased blood pressure (BP) drop and postural sway., Methods: Fourteen healthy individuals (eight women) performed two orthostatic tests under thermal reference (TC; ~ 24 ºC) and HOT (~ 38 ºC) conditions. The center-of-pressure (COP) displacements and the electromyography (EMG) activity of the calf muscles (medial gastrocnemius and tibialis anterior) were recorded during the initial orthostasis (ORT onset) after the supine-to-stand challenge. At the same period, BP (beat-to-beat) was continuously monitored, and supine-to-stand variations (∆%) were calculated. Sublingual temperature (Tsl) was measured as a surrogate of internal temperature., Results: Tsl increased in HOT compared to TC (TC 36.5 ± 0.3 vs. HOT 36.7 ± 0.3 ºC; p < 0.01). COP distance was greater in HOT compared to TC condition (TC 596.6 ± 242.4 vs. HOT 680.2 ± 249.1 mm; p < 0.01). EMG activity of the gastrocnemius decreased in HOT compared to TC condition (TC 95.5 ± 19.8 vs. HOT 78.4 ± 22.8%mV; p = 0.02). EMG of tibialis did not change between TC and HOT (TC 83.5 ± 42.9 vs. HOT 66.1 ± 31.9% mV; p = 0.29). BP showed a greater fall in HOT compared to TC condition (∆%TC - 24.5 ± 13.2 vs. ∆%HOT - 33.2 ± 20.2%; p = 0.01)., Conclusion: Heat stress causes a greater fall in blood pressure and a reduction in musculoskeletal pump activity during orthostatic onset. These effects could be potential mechanisms that underlie augmented postural instability under a heated environment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although there has been a large increase in the number of extensive macular atrophy with pseudodrusen (EMAP) cases, the basic aspects of this disease remain unknown. Brazilian patients have a common past history of rheumatic fever (RF) and/or benzathine penicillin (BP) treatment possibly related to the disease. We analyzed how RF and BP might be correlated with EMAP in Brazilian patients., Design: Observational, retrospective, case-control study., Methods: The databases of three private eye clinics in Brazil were searched for patients with an EMAP-like appearance. Each patient was asked about a previous history of RF and/or long-term use of BP. Patients underwent best-corrected visual acuity (BCVA) measurement, color fundus imaging, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT) imaging, and electroretinography (ERG). The following characteristics were analyzed: subretinal drusenoid deposits (SDD), pigment mottling, retinal pigment epithelial/basement membrane (RPE/BM) separation, outer retinal or RPE atrophy, and identification of a paving stone-like appearance. The choroidal thickness was measured using enhanced depth imaging OCT. The central atrophic area was measured manually on ultra-wide-field FAF., Results: A total of 154 eyes of 77 patients (women, 66.2%; mean age, 58.6 years) with EMAP were included; 90.9% of patients were diagnosed with RF; 94.8% had been treated with BP and treatment was started at an average age of 7.3 years (mean duration, 11.8 years). The treatment duration was significant for the area of atrophy (P = 0.027) in which each 1-year increase in treatment duration led to an average reduction of 6.91 mm 2 in area. The age at diagnosis of RF was significant (P = 0.026) for SDD. The increase of 1 year in the diagnosis of RF (late disease) led to a reduction of 24% in the chance of central SDD being present. On OCT, 65.5% eyes had SDD and more than 70% had a split RPE/BM and outer retinal or RPE atrophy. The choroidal thickness in patients with EMAP was significantly (P < 0.001) thinner than the control group. The ERG was abnormal in all eyes., Conclusion: These findings may suggest a relation between RF and EMAP in Brazilian patients. Patients with EMAP should be questioned about a history of RF., (© 2024. The Author(s).)

Fatigue is a symptom frequently complained about by older people but unfortunately poorly understood given its subjectivity and the lack of a gold standard for its assessment. The purpose of this study was therefore to preliminarily explore agreement among four different fatigue scales in a sample of persons with extreme longevity (PEL), their direct offsprings (DO), and controls (CO) matched for age and sex with DO. κ statistics was used to quantify agreement among four different fatigue scales. The agreement ranged from mild to substantial and almost perfect agreement depending on the group considered. The highest agreement was found between the Multidimensional Assessment of Fatigue scale and the Short Form Health Survey-36-Vitality Subscale in the PEL group (κ 0.820; 95 % CI 0.471-0.947). These preliminary findings may serve as a guide in selecting the most feasible instrument to assess fatigue in future large-scale research and clinical activities involving older people., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Although both aging and menopause influence cardiovascular autonomic control, the effect of menopause per se remains unclear. The current study was undertaken to test the hypothesis that post-menopausal women (PMW) have a blunted cardiovascular autonomic adjustment to active standing compared to pre-menopausal women. Thus, we compared the heart rate variability (HRV) indexes from supine (SUP) to orthostatic (ORT) positions among young women (YW), young men (YM), older men (OM), and PMW., Methods: The participants rested for 10 min in SUP and then stood up and remained for 5 min in ORT. ECG was continuously recorded, and R-R time series of about 300 beats were analyzed using linear (spectral analysis) and non-linear (symbolic analysis) methods. The variation from SUP to ORT was calculated ( Δ  = ORT-SUP) for each HRV index., Results: In SUP, no difference was found for any HRV index among groups. However, Δ 0V% and Δ LFn (cardiac sympathetic modulation) were reduced in PWM compared to all groups (OM, YW, and YM), while Δ 2UV% and Δ HFn (cardiac vagal modulation) were reduced in PMW than the younger group (YW and YM). No differences were found among the male groups (OM and YM)., Discussion: In light of our results, the cardiac autonomic dynamic response to orthostatic stress is blunted in post-menopausal women compared to younger women and older men, a finding that might be influenced not only by aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Scatà, Ferreira, Padilha, Carandina, Asnaghi, Bellocchi, Tobaldini, Montano, Soares and Rodrigues.)

Tabanidae are considered a nuisance to humans, wild animals, and livestock due to their painful, annoying, and insistent biting. Tabanids transmit some pathogens and parasites biologically and mechanically. In humans, there are relatively few pathogens transmitted regularly. Still, tabanids serve as vectors of a number of disease agents of animals, including viruses, bacteria, protozoans, and nematodes. They are more abundant in tropical and humid regions, and their seasonal patterns are affected by habitat changes such as deforestation and fragmentation. Here, we analyze the tabanid fauna in Monte Negro, a central municipality of Rondônia, Brazil, comparing abundance, richness, and diversity in forest and pasture habitats. Traps were set for 5 days a month for 12 consecutive months. We also examined how abiotic factors (humidity, temperature, and rainfall) affected the abundance, diversity, and richness and the effectiveness of Malaise and Nzi traps as sample methods. The influence of climatic variables on the richness and abundance of the species was tested using generalized linear models, and we used non-parametric dimensional scaling (nMDS) for analysis of species composition and diversity in different traps and environments. We collect 1032 specimens of 25 species. The most abundant species were Tabanus antarcticus, Dichelacera tetradelta, Tabanus mucronatus, and Leucotabanus albovarius. Forest habitats had the highest number of tabanids, followed by pasture and the anthropized area, and there was no significant difference regarding the effectiveness of the Malaise and Nzi traps. The study provides new information on the distribution and ecology of tabanids in Brazil., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tabanidae (Diptera), popularly known as horse flies, is an important vector group. This is the first study to ascertain the abundance and diversity of horse flies in horses at the cerrado biome of the state of Tocantins, Brazil. Collecting took place in typical Cerrado, and sampling occurred in the dry and rainy seasons. The horseflies were collected from horses using an entomological net. A total of 249 individuals were collected and spread over 25 species. The prevalent species were Stypommisa aripuana (25.8%) and Catachlorops rufescens (6.4%), in the dry period, and Fidena lissorhina (22.5%), Tabanus occidentalis var. dorsovittatus (10%) and Poeciloderas quadripunctatus (6.4%), in the rainy season. The results suggest that tabanids attack horses throughout the dry and rainy seasons, posing a constant threat to their health in the Cerrado of Tocantins.

Background: Rett syndrome (RTT) is a rare neurological disorder primarily associated with mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The syndrome is characterized by cognitive, social, and physical impairments, as well as sleep disorders and epilepsy. Notably, dysfunction of the autonomic nervous system is a key feature of the syndrome. Although Heart Rate Variability (HRV) has been used to investigate autonomic nervous system dysfunction in RTT during wakefulness, there is still a significant lack of information regarding the same during sleep. Therefore, our aim was to investigate cardiovascular autonomic modulation during sleep in subjects with RTT compared to an age-matched healthy control group (HC)., Method: A complete overnight polysomnographic (PSG) recording was obtained from 11 patients with Rett syndrome (all females, 10 ± 4 years old) and 11 HC (all females, 11 ± 4 years old; p = 0.48). Electrocardiogram and breathing data were extracted from PSG and divided into wake, non-REM, and REM sleep stages. Cardiac autonomic control was assessed using symbolic non-linear heart rate variability analysis. The symbolic analysis identified three patterns: 0 V% (sympathetic), 2UV%, and 2LV% (vagal)., Results: The 0 V% was higher in the RTT group than in the HC group during wake, non-REM, and REM stages (p < 0.01), while the 2LV and 2UV% were lower during wake and sleep stages (p < 0.01). However, the 0 V% increased similarly from the wake to the REM stage in both RTT and HC groups., Conclusions: Therefore, the sympatho-vagal balance shifted towards sympathetic predominance and vagal withdrawal during wake and sleep in RTT, although cardiac autonomic dynamics were preserved during sleep., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Horse fly females (Diptera, Tabanidae) are hematophagous and can vector pathogens that affect livestock. Complexes of cryptic species are common in Tabanidae, as exemplified by some species of Tabanus, including Tabanus triangulum and Tabanus occidentalis, both prevalent in the Southern region of Brazil. In this study, geometric morphometrics were employed to ascertain the wing venation in species identification. It was demonstrated that this tool effectively differentiates T. triangulum from T. occidentalis in the coastal plain of Rio Grande do Sul state, situated within the Pampa biome. The results indicate that T. triangulum and T. occidentalis occupy distinct regions of the morphological space, allowing their precise identification through geometric morphometrics, which is fast, affordable, and easy to implement.

Hypoxia increases inspiratory muscle work and consequently contributes to a reduction in exercise performance. We evaluate the effects of inspiratory muscle warm-up (IMW) on a 10 km cycling time trial in normoxia (NOR) and hypoxia (HYP). Eight cyclists performed four time trial sessions, two in HYP (FiO 2 : 0.145) and two in NOR (FiO 2 : 0.209), of which one was with IMW (set at 40% of maximal inspiratory pressure-MIP) and the other was with the placebo effect (PLA: set at 15% MIP). Time trials were unchanged by IMW (NOR IMW : 893.8 ± 31.5 vs. NOR PLA : 925.5 ± 51.0 s; HYP IMW : 976.8 ± 34.2 vs. HYP PLA : 1008.3 ± 56.0 s; p > 0.05), while ventilation was higher in HYP IMW (107.7 ± 18.3) than HYP PLA (100.1 ± 18.9 L.min -1 ; p ≤ 0.05), and SpO 2 was lower (HYP IMW : 73 ± 6 vs. HYP PLA : 76 ± 6%; p ≤ 0.05). A post-exercise-induced reduction in inspiratory strength was correlated with exercise elapsed time during IMW sessions (HYP IMW : r = -0.79; p ≤ 0.05; NOR IMW : r = -0.70; p ≤ 0.05). IMW did not improve the 10 km time trial performance under normoxia and hypoxia.

People with extreme longevity represent a unique model to study the biology of aging. Unfortunately, their inclusion in research projects is challenging with the consequent lack of evidence and the need to rely on small convenience samples. Given the growing global aging population, especially in the segment of the oldest old (i.e., aged 90 and older), research in this population has become crucial. Furthermore, by studying the characteristics of extremely longeval persons, it might be possible to 1) better understand the mechanisms of aging, and 2) identify endogenous or exogenous factors contributing to a long life. The design and implementation of research activities in the oldest people need special consideration and a pragmatic approach. Possible implementable solutions and suggestions are provided from experience gained during the conduction of the FAtigue in CEnTenarians (FACET) study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Systemic sclerosis (SSc) is an autoimmune disease with health-related quality of life (HRQoL) high impairment. Pain is of paramount importance to be targeted by therapeutical approaches. Our study aim was to perform an add-on device-based non-invasive neuromodulatory treatment through transcutaneous auricular vagal nerve stimulation (tVNS) in patients with SSc, assessing its effects on pain as primary endpoint and on inflammation, cardiovascular autonomic control and HRQoL., Methods: Thirty-two patients with SSc were enrolled based on reported pain assessed through Numeric Rating Scale (NRS). Twenty-one (90% with limited cutaneous SSc) completed a randomised, cross-over, patient-blind trial, in which interventional and active control were used in random order for 4 weeks, interspersed with 4 weeks washout. NRS, Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Item4 for pain interference, heart rate variability (HRV), serum cytokines and HRQoL questionnaires (Health Assessment Questionnaire, Patient Health Questionnaire-9, University of California, Los Angeles Gastrointestinal Tract, Pittsburgh Sleep Quality Index) were assessed at baseline, at T1 (after 1 month of tVNS or active control), at T2 (after washout) and at T3 (after 1 month of active control or tVNS). T-test for paired data and Wilcoxon signed-rank test for non-normally distributed parameters were performed to compare the effect of tVNS and active control., Results: NRS pain was significantly reduced by tVNS and not by active control (Mean±SD: -27.7%±21.3% vs -7.7%±26.3%, p=0.002). Interleukin-6 was downregulated in tVNS versus active control (p=0.029). No significant differences were observed in tVNS versus active control for PROMIS-29 Item4, QoL scales and HRV with both spectral and symbolic analyses., Conclusion: tVNS demonstrated to be a safe and non-invasive add-on tool to reduce pain in SSc., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Prolonged rowing exercise sessions are often prescribed considering competitive training schedules, and under hostile environments (e.g., heated ambient). The study aimed to investigate the effect of heat stress (HS) on physical performance, Lactate concentration ([Lac]), and cardiorespiratory responses during prolonged exercise sessions in competitive rowers. Twelve rowers performed preliminary exercise tests (2-km test and five-step incremental lactate test) to assess the target workload intensity corresponding to a 2.5 mmol . L -1 of [Lac]. On two separate days, participants were enrolled in two exercise sessions of 12 km in a rowing machine under HS (∼30 °C) and thermal comfort (TC 22 °C) conditions. Heart rate (HR), stroke volume (SV), cardiac output (CO), oxygen uptake (VO 2 ), [Lac], and the rating of perceptual exertion (RPE) were obtained. From baseline, HS increased the maximum temperature of the face compared to TC. Workload and VO 2 reduced while RPE increased at 9- and 12-km of rowing exercise under HS compared to TC. From baseline to the last stage of exercise, HS shifted SV downwards and HR upwards compared to TC. Consequently, CO did not change between thermal conditions (TC vs. HS). Therefore, HS provokes a cardiovascular drift during prolonged rowing in comparison to TC. The last stages of prolonged rowing sessions under HS seem to be critical to physical performance and relative perceptual of effort in rowers., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision. Pathogenic variants in six genes encoding proteins composing the cone phototransduction cascade ( CNGA3 , CNGB3 , PDE6C , PDE6H , GNAT2 ) and of the unfolded protein response ( ATF6 ) have been related to ACHM cases, while CNGA3 and CNGB3 alone are responsible for most cases. Herein, we provide a clinical and molecular overview of 42 Brazilian patients from 38 families affected with ACHM related to biallelic pathogenic variants in the CNGA3 and CNGB3 genes. Patients' genotype and phenotype were retrospectively evaluated. The majority of CNGA3 variants were missense, and the most prevalent CNGB3 variant was c.1148delC (p.Thr383Ilefs*13), resulting in a frameshift and premature stop codon, which is compatible with previous publications in the literature. A novel variant c.1893T>A (p.Tyr631*) in the CNGB3 gene is reported for the first time in this study. A great variability in morphologic findings was observed in our patients, although no consistent correlation with age and disease stage in OCT foveal morphology was found. The better understanding of the genetic variants landscape in the Brazilian population will help in the diagnosis of this disease.

Atrial fibrillation (AF) is the most common type of sustained arrhythmia. The numerous gaps concerning the knowledge of its mechanism make improving clinical management difficult. As omics technologies allow more comprehensive insight into biology and disease at a molecular level, bioinformatics encompasses valuable tools for studying systems biology, as well as combining and modeling multi-omics data and networks. Network medicine is a subarea of network biology where disease traits are considered perturbations within the interactome. With this approach, potential disease drivers can be revealed, and the effect of drugs, novel or repurposed, used alone or in combination, may be studied. Thus, this work aims to review AF pathology from a network medicine perspective, helping researchers to comprehend the disease more deeply. Essential concepts involved in network medicine are highlighted, and specific research applying network medicine to study AF is discussed. Additionally, data integration through literature mining and bioinformatics tools, with network building, is exemplified. Together, all of the data show the substantial role of structural remodeling, the immune system, and inflammation in this disease etiology. Despite this, there are still gaps to be filled about AF.

Rett syndrome (RTT) is a rare and severe neurological disorder mainly affecting females, usually linked to methyl-CpG-binding protein 2 (MECP2) gene mutations. Manifestations of RTT typically include loss of purposeful hand skills, gait and motor abnormalities, loss of spoken language, stereotypic hand movements, epilepsy, and autonomic dysfunction. Patients with RTT have a higher incidence of sudden death than the general population. Literature data indicate an uncoupling between measures of breathing and heart rate control that could offer insight into the mechanisms that lead to greater vulnerability to sudden death. Understanding the neural mechanisms of autonomic dysfunction and its correlation with sudden death is essential for patient care. Experimental evidence for increased sympathetic or reduced vagal modulation to the heart has spurred efforts to develop quantitative markers of cardiac autonomic profile. Heart rate variability (HRV) has emerged as a valuable non-invasive test to estimate the modulation of sympathetic and parasympathetic branches of the autonomic nervous system (ANS) to the heart. This review aims to provide an overview of the current knowledge on autonomic dysfunction and, in particular, to assess whether HRV parameters can help unravel patterns of cardiac autonomic dysregulation in patients with RTT. Literature data show reduced global HRV (total spectral power and R-R mean) and a shifted sympatho-vagal balance toward sympathetic predominance and vagal withdrawal in patients with RTT compared to controls. In addition, correlations between HRV and genotype and phenotype features or neurochemical changes were investigated. The data reported in this review suggest an important impairment in sympatho-vagal balance, supporting possible future research scenarios, targeting ANS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cordani, Tobaldini, Rodrigues, Giambersio, Veneruso, Chiarella, Disma, De Grandis, Toschi-Dias, Furlan, Carandina, Prato, Nobili and Montano.)

Background: Post-menopausal women have impaired cardiorespiratory responses to exercise compared to young women. Exercise training may counterbalance impairments, but the time-dependent effects of exercise training remain unclear. The current study aims to investigate the effects of rowing training on maximal aerobic capacity and time-course cardiorespiratory adaptations in older women., Methods: Female participants ( n = 23) were randomly allocated to the experimental group (EXP; n = 23; 66 ± 5 years old) enrolled in rowing exercise training and control group (CON; n = 10; 64 ± 4 years old). The cardiopulmonary exercise test (CET) was performed in a cycle ergometer pre- and post-interventions. Oxygen uptake (VO 2 ), stroke volume (SV), cardiac output (CO), and HR were recorded during CET and analyzed at the peak of the exercise. HR was monitored during exercise recovery, and the index of HRR was calculated by ΔHRR (HR peak -HR one-minute recovery). Every two weeks, Rowing Stepwise Exercise (RSE) in a rowing machine was performed to track specific adaptations to the exercise modality. HR was continuously recorded during RSE and corrected for the average power of each step (HR/watts). The rowing training protocol consisted of three weekly sessions of 30 min at an intensity corresponding to 60-80% of peak HR for ten weeks., Results: Rowing exercise training increased VO 2 , SV, and CO at the peak of the CET, and ΔHRR. Increased workload (W) and reduced HR response to a greater achieved workload (HR/W) during RSE were observed after six weeks of training., Conclusions: Rowing exercise training is a feasible method to improve cardiorespiratory performance, vagal reactivation and heart rate adjustments to exercise in older women.

We hypothesized that inspiratory muscle training (IMT) increases the respiratory-induced low-frequency oscillations of mean blood pressure (MBP) and middle cerebral artery blood velocity (MCAv), upregulating cerebrovascular function in older women. Firstly, participants were recorded with free-breathing (FB) and then breathed at a slow-paced frequency (0.1 Hz; DB test) supported by sonorous metronome feedback. Blood pressure was recorded using finger photoplethysmography method, ECG, and respiration using a thoracic belt. To obtain the MCAv a transcranial ultrasound Doppler device was used. Spectral analysis of MBP, R-R intervals, and mean MCAv time series was obtained by an autoregressive model. The transfer function analysis (TFA) was employed to calculate the coherence, gain, and phase. After that, older women were enrolled in a randomized controlled protocol, the IMT-group (n = 8; 64 ± 3 years-old) performed IMT at 50 % of maximal inspiratory pressure (MIP), and Sham-group, a placebo training at 5 % MIP (Sham-group; n = 6; 66 ± 3 years-old). Participants breathed against an inspiratory resistance twice a day for 4-weeks. DB test is repeated post IMT and Sham interventions. IMT-group, compared to Sham-group, augmented tidal volume responses to DB (Sham-group 1.03 ± 0.41 vs. IMT-group 1.61 ± 0.56 L; p = 0.04), increased respiratory-induced MBP (Sham-group 26.37 ± 4.46 vs. IMT-group 48.21 ± 3.15 mmHg 2 ; p = 0.04) and MCAv (Sham-group 14.16 ± 31.26 vs. IMT-group 79.90 ± 21.76 cm 2 s -2 ; p = 0.03) slow oscillations, and reduced TFA gain (Sham-group 2.46 ± 1.32 vs. IMT-group 1.78 ± 1.30 cm·s -1. mmHg -1 ; p = 0.01). Our findings suggest that IMT increases the respiratory-induced oscillations in MBP and MCAv signals and reduces TFA gain. It seems compatible with an improved dynamic cerebrovascular regulation following IMT in older women., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective. To conduct a systematic review of the possible effects of passive heating protocols on cardiovascular autonomic control in healthy individuals. Approach. The studies were obtained from MEDLINE (PubMed), LILACS (BVS), EUROPE PMC (PMC), and SCOPUS databases, simultaneously. Studies were considered eligible if they employed passive heating protocols and investigated cardiovascular autonomic control by spontaneous methods, such as heart rate variability (HRV), systolic blood pressure variability (SBPV), and baroreflex sensitivity (BRS), in healthy adults. The revised Cochrane risk-of-bias tool (RoB-2) was used to assess the risk of bias in each study. Main results. Twenty-seven studies were included in the qualitative synthesis. Whole-body heating protocols caused a reduction in cardiac vagal modulation in 14 studies, and two studies reported both increased sympathetic modulation and vagal withdrawal. Contrariwise, local-heating protocols and sauna bathing seem to increase cardiac vagal modulation. A reduction of BRS was reported in most of the studies that used whole-body heating protocols. However, heating effects on BRS remain controversial due to methodological differences among baroreflex analysis and heating protocols. Significance. Whole-body heat stress may increase sympathetic and reduce vagal modulation to the heart in healthy adults. On the other hand, local-heating therapy and sauna bathing seem to increase cardiac vagal modulation, opposing sympathetic modulation. Nonetheless, further studies should investigate acute and chronic effects of thermal therapy on cardiovascular autonomic control., (© 2023 Institute of Physics and Engineering in Medicine.)

Cerebral autoregulation (CA) refers to the control of cerebral tissue blood flow (CBF) in response to changes in perfusion pressure. Due to the challenges of measuring intracranial pressure, CA is often described as the relationship between mean arterial pressure (MAP) and CBF. Dynamic CA (dCA) can be assessed using multiple techniques, with transfer function analysis (TFA) being the most common. A 2016 white paper by members of an international Cerebrovascular Research Network (CARNet) that is focused on CA strove to improve TFA standardization by way of introducing data acquisition, analysis, and reporting guidelines. Since then, additional evidence has allowed for the improvement and refinement of the original recommendations, as well as for the inclusion of new guidelines to reflect recent advances in the field. This second edition of the white paper contains more robust, evidence-based recommendations, which have been expanded to address current streams of inquiry, including optimizing MAP variability, acquiring CBF estimates from alternative methods, estimating alternative dCA metrics, and incorporating dCA quantification into clinical trials. Implementation of these new and revised recommendations is important to improve the reliability and reproducibility of dCA studies, and to facilitate inter-institutional collaboration and the comparison of results between studies.

Tabanidae is one of the most diverse families of hematophagous dipterans. Tabanids, in general, are mechanical vectors of some pathogens. Given the vector importance and the lack of knowledge of the tabanid fauna in horses in Amazon Forest fragments of the state of Rondônia, this work aimed to determine the season that the different species of horse flies prefer to carryout hematophagy on horses and verify whether the horse fly community remains the same throughout the year. The sampling areas for tabanid captures were in the municipality of Monte Negro, Western Amazon, Brazil. Four new occurrences were recorded for the state of Rondônia: Stenotabanus albilinearis, Tabanus fuscofasciatus, T. macquarti and T. restrepoensis, which increases the number of species for the state to 109. The horse flies were most frequently collected on the hind leg (43.15%) and front leg (31.11%), followed by the belly (7.41%) and the ear (5.18%). In the other anatomical regions, the collection frequency was 13.15% of the remaining individuals., Competing Interests: Declaration of Competing Interest Tabanidae (Diptera) captured on horses in Amazon Forest fragments of the State of Rondônia, Brazil. The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2022. Published by Elsevier B.V.)

Fighter pilots (FP) are exposed to flight accelerations and stressful situations that defy cardiovascular control during and after flight. FP presents a smaller adjustment in sympatho-vagal balance during tilt test after flight compared to baseline, suggesting a huge impact of flight on autonomic modulation to the heart. We undertake to test the hypothesis that FP will have a smaller vagal reentrance and lower sympathetic withdrawal during the recovery at the supine position after a prolonged active standing test that mimics flight hemodynamic demands. Twenty-one military personnel (20-34 years old), composed of 9 FP and 12 non-pilots (NP) matched by age, V̉O 2max and body mass index were enroled in the experimental protocol. R-R intervals were continuously recorded in the supine position for 15 min (SUP baseline ), during the prolonged active standing test (45 min) windowed in six 5 min time frames (from ORT1 to ORT6), and a recovery period in the supine position for 15 min (SUP recovery ). Heart rate variability was performed by spectral analysis to obtain the normalized low (LFn) and high (HFn) frequency components. The variation (Δ) from baseline (Δ = ORT6 - SUP baseline ) and from recovery (Δ = SUP recovery -ORT6) periods were calculated. FP had a smaller ΔLFn (sympathetic mediated) and ΔHFn (vagal meditated) during recovery after active standing as compared to NP. Both groups showed similar changes in ΔLFn and ΔHFn during orthostatic stress compared to baseline, with no differences over time. Therefore, FP show a smaller vagal reentrance and a lower sympathetic reduction during recovery at supine following active standing compared to NP., (© 2022 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Anaplasma marginale is transmitted biologically by infected ticks or mechanically by biting flies and contaminated fomites. In tick-free areas, such as southern Uruguay, horseflies could be the principal vectors of this pathogen for bovines, causing anaplasmosis. The objective of this work was to detect the presence of A. marginale by MSP-5 PCR and Sanger sequencing in the most prevalent species of horseflies obtained using different collection methods in Colonia, Tacuarembó and Paysandú, Uruguay. Eight horsefly species were tested (Dasybasis missionum, Poeciloderas lindneri, Tabanus campestris, T. claripennis, T. fuscofasciatus, T. platensis, T. tacuaremboensis and T. triangulum); four species were found to be positive for A. marginale, with D. missionum and P. lindneri having the most frequent infections, while only one individual each of T. fuscofasciatus and T. tacuaremboensis was positive. Both D. missionum and P. lindneri were positive for A. marginale in tick-free areas, and the implications are discussed in this report., (© 2022. The Author(s).)

Systemic sclerosis (SSc) patients often present cardiovascular autonomic dysfunction, which is associated with the risk of arrhythmic complications and mortality. However, little is known regarding the progression of cardiac autonomic impairment over time. We aimed to evaluate the cardiac autonomic modulation among SSc with limited cutaneous (lcSSc), diffuse cutaneous (dcSSc) subset, and age-matched healthy control (HC) at baseline (t0) and five-year follow-up (t1). In this follow-up study, ECG was recorded at t0 and t1 in twenty-four SSc patients (dcSSc; n = 11 and lcSSc; n = 13) and 11 HC. The heart rate variability (HRV) analysis was conducted. The spectral analysis identified two oscillatory components, low frequency (LF) and high frequency (HF), and the sympatho-vagal balance was assessed by the LF/HF ratio. The LF/HF increased (p = 0.03), and HF reduced at t1 compared to t0 in dcSSc (p = 0.03), which did not occur in the lcSSc and HC groups. Otherwise, both lcSSc and dcSSc groups presented augmented LF/HF at t0 and t1 compared to HC (p < 0.01). In conclusion, a worsening of cardiac autonomic dysfunction is related to the dcSSc subset, in which a more extent of skin fibrosis and internal organs fibrosis is present.

The heated environment shifts the sympatho-vagal balance toward sympathetic predominance and vagal withdrawal. Women's heart is more reliant on vagal autonomic control, while men's heart is more dependent on sympathetic control. However, sex differences in cardiovascular autonomic responses to heat stress remain unknown. We aimed to investigate the cardiovascular autonomic regulation under heat stress between sexes. Thirty-two young participants (27 ± 4 years old; 16 women) were enrolled in a single visit, resting for 30min at baseline (thermal reference condition TC; ∼24°C) and 30min under a heated environment (HOT; ∼38°C). Blood pressure (BP), skin temperature, electrocardiogram, and respiratory oscillations were continuously recorded. The heart rate variability (HRV) was assessed by spectral analysis (low-frequency [LFnu; sympathetic and vagal] and high-frequency [HFnu; vagal]), and symbolic analysis (0 V% [sympathetic] and 2UV%, and 2LV% [vagal]). The spontaneous baroreflex sensitivity (BRS) was calculated by the gain between BP and R-R within the LF band (αLF). The estimated maximal aerobic capacity and body surface area were employed as covariates in sex comparisons. The effects of HOT were the following: 1) Women have a greater cardiac vagal withdrawal to heat stress compared to men; 2) Sex differences on cardiac autonomic response to heat stress exist after controlling for the effect of estimated physical fitness and body surface area. Therefore, heat stress provokes a higher vagal withdrawal to the heart in women compared to men. It could be attributed to sex per se since significant differences between men and women were not modified after covariate analysis., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 Informa UK Limited, trading as Taylor & Francis Group.)

Objective: We investigated sex differences in blood pressure (BP) response to transcutaneous electrical nerve stimulation (TENS) during orthostatic stress (ORT)., Methods: Seventeen healthy young adults (males = 9; females = 8) underwent TENS or SHAM stimulus applied in the cervicothoracic region for 30 min in the supine position followed by 10 min in the orthostatic position. Electrocardiogram and BP were continuously recorded at rest and during ORT. Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were calculated from the BP signal., Results: Orthostatic challenge decreased BP similarly for both sexes during ORT, a deeper drop in CO and a slight increase in heart rate were found in women compared with men ( P = 0.03 and 0.05, respectively). TENS evoked a pronounced fall in SBP in men compared with the SHAM condition ( P < 0.05). TENS has no effect on SBP in women compared with the SHAM condition., Conclusion: This finding suggests a possible modulatory effect by one cervicothoracic TENS session on sympathetic tonus in healthy men., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Sedentarism and chronic non-communicable diseases have been a worldwide health problem that is drastically exacerbated by the COVID-19 pandemic social impacts. Home-based exercises are widely encouraged during social isolation to counterbalance the physical inactive impacts. Although, in the context of hypertension, are home-based exercises effective in blood pressure controlling? Our objective is to conduct a systematic review of high-quality controlled trials comparing the possible effects of different types of home-based exercises in hypertensive patients. The literature search was carried out in three scientific databases: Medline, Europe PMC, and Lilacs. Articles were included following three criteria: analyzing the effect of home-based exercise programs on blood pressure in treated and untreated hypertensive patients; exercises must perform at home and on the frequency, intensity, time, and type (FITT) principle, and the articles were published in English. From the qualitative analysis of 27 original trials screened through 451 identified studies, the main results are the following: 1) both endurance, isometric strength, and respiratory home-based exercise programs were efficient to decrease blood pressure in hypertensive patients; 2) differences in methodological approaches regarding FITT components, distinct blood pressure values at baseline and specific underlying mechanisms must be considered as a potential bias of each home-based interventions. In conclusion, endurance, isometric strength, and breathing home-based programs seems to be effective to reduce blood pressure in hypertensive patients. However, further randomized controlled trials and mechanistic studies must be performing to guide evidence-based recommendations of home-based exercises as antihypertensive therapy., (© 2022. The Author(s).)

Despite several studies that have been investigated physical inactivity and age-related effects on orthostatic tolerance, impaired hemodynamics and postural balance responses to orthostatic stress are incorrectly attributed to aging or sedentarism alone. The isolated effects from aging and sedentarism should be investigated through comparative studies between senior athletes and age-matched controls, and physical activity assessments on aging follow-up studies. On the other hand, bed rest and space flight studies mimic accelerated physical inactivity or disuse, which is not the same physiological decline provoked by aging alone. Thus, the elementary question is: could orthostatic intolerance be attributed to aging or physical inactivity? The main purpose of this review is to provide an overview of possible mechanisms underlying orthostatic tolerance contrasting the paradigm of aging and/or physical inactivity. The key points of this review are the following: (1) to counterpoint all relevant literature on physiological aspects of orthostatic tolerance; (2) to explore the mechanistic aspects underneath the cerebrovascular, cardiorespiratory, and postural determinants of orthostatic tolerance; and (3) examine non-pharmacological interventions with the potential to counterbalance the physical inactivity and aging effects. To date, the orthostatic intolerance cannot be attributed exclusively with aging since physical inactivity plays an important role in postural balance, neurovascular and cardiorespiratory responses to orthostatic stress. These physiological determinates should be interpreted within an integrative approach of orthostatic tolerance, that considers the interdependence between physiological systems in a closed-loop model. Based on this multisystem approach, acute and chronic countermeasures may combat aging and sedentarism effects on orthostatic tolerance., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The current study was undertaken to test the hypothesis that systemic sclerosis (SSc) patients with higher systolic pulmonary arterial pressures (PAPs) present a blunted cardiac autonomic modulation and a pro-inflammatory profile. Thirty-nine SSc patients were enrolled (mean age 57 ± 11 years). ECG and respiration were recorded in the supine (SUP) position and during the active standing (ORT). Heart rate variability (HRV) analysis was performed on samples of 300 beats. The symbolic analysis identified three patterns, 0V%, (sympathetic) and 2UV% and 2LV%, (vagal). The %ΔORT was calculated from the differences between HRV in ORT and SUP, normalized (%) by the HRV values at rest. The PAPs was obtained non-invasively through echocardiography. For the inter-group analysis, participants were allocated in groups with higher (+PAPs ≥ median) and lower PAPs (-PAPs < median) values. At rest, the cardiac sympathetic modulation (represented by 0V%) was positively correlated with PAPs, while parasympathetic modulation (represented by 2LV%) was negatively correlated with PAPs. The dynamic response to ORT (represented by Δ0V% and Δ2LV%), sympathetic and parasympathetic were negatively and positively correlated with PAPs, respectively. The +PAPs group presented a higher inflammatory status and a blunted cardiac autonomic response to ORT (↓Δ0V% and ↑Δ2LV%) compared to the -PAPs group. These findings suggest an interplay among cardiac autonomic control, inflammatory status, and cardiopulmonary mechanics that should be considered for the assessment, monitoring, and treatment of SSc patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rodrigues, Vicenzi, Bellocchi, Beretta, Carandina, Tobaldini, Carugo and Montano.)

Several studies have described the effects of human tumor necrosis factor alpha (hTNF-α) on Schistosoma mansoni. hTNF-α affects the worm's development, metabolism, egg-laying, gene expression and protein phosphorylation. The available data on the influence of hTNF-α on egg-laying in S. mansoni are controversial, but understanding the mechanism of egg-laying regulation in this species is essential in combating schistosomiasis. We characterized the effects of in vitro treatment of S. mansoni adult worms with different doses of hTNF-α (5, 20 and 40 ng/ml) for 5 days. We explored the effects on egg-laying rate, glucose levels, ATP metabolism, and messenger RNA (mRNA) expression levels of lactate dehydrogenase, glucose transporters and the parasite gene which acts as an hTNF-α receptor, SmTNFR. hTNF-α influenced egg-laying in a time- and dose-dependent manner: at a dose of 40 ng/ml, egg-laying increased on day 2 and decreased on days 3 and 4; at 20 ng/ml, egg-laying decreased on day 3; while at 5 ng/ml, egg-laying decreased on day 4. The total number of eggs produced was not affected by the different treatments, but the egg-laying dynamics were: the median egg-laying time decreased significantly with treatment, and egg developmental stages and size were also affected. At 5 and 20 ng/ml hTNF-α, lactate production diminished on day 3 up to day 5, while glucose uptake increased on day 5. At 40 ng/ml, glucose uptake diminished on day 1 up to day 3, while ATP accumulation was detected on day 5. No significant changes in mRNA expression were detected in any of the treatments. We found that crosstalk involving hTNF-α and parasite signaling plays a role in the fine-scale regulation of the worm's metabolism and physiology, and points to new strategies for disease control., (© 2022. The Author(s).)

Evidence from clinical practice suggests that PD patients with the Glucocerebrosidase gene mutations (GBA-PD) are characterized by more severe dysautonomic symptoms than patients with idiopathic PD (iPD). Therefore, an accurate assessment of cardiovascular autonomic control (CAC) is necessary to clarify the role of GBA mutations in the pathophysiology of PD. We evaluated the CAC at rest and during orthostatic challenge of 15 iPD, 15 GBA-PD and 15 healthy controls (CTR). ECG and respiration were recorded in supine position and during active standing. The analysis of Heart Rate Variability (HRV) was performed on ECG recordings using two different approaches, linear spectral analysis and non-linear symbolic analysis. GBA-PD patients presented more frequently an akinetic-rigid phenotype and cognitive dysfunction than iPD patients. Both iPD and GBA-PD group were characterized by a lower spectral HRV than CTR group. At rest, the GBA-PD group was characterized by a lower parasympathetic modulation and a shift of the sympathovagal balance toward a sympathetic predominance compared to the CTR group. Moreover, the GBA-PD patients presented a lower HR increment and a lower or absent reduction of the vagal modulation in response to the active standing than iPD patients. Lastly, the cardiovascular autonomic dysfunction in PD patients was associated with longer disease duration, and with the occurrence of REM sleep behavior disorder and constipation. Our findings suggest a more severe impairment of the CAC in PD patients with GBA mutations. These results and further studies on the role of GBA mutations could allow a stratification based on cardiovascular risk in PD patients and the implementation of specific prevention programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Carandina, Lazzeri, Rodrigues, Franco, Monfrini, Arienti, Frattini, Trezzi, da Silva Soares, Bellocchi, Furlan, Montano, Di Fonzo and Tobaldini.)

Purpose: The species of the genus Trypanosoma are carried and transmitted by horseflies parasitizing a high diversity of vertebrates. In the Coastal Plain of Rio Grande do Sul, southern Brazil, Tabanus triangulum is the most abundant species and, similarly to the other species of horseflies, there is little knowledge about its vector competence. Therefore, this study aimed to screen the field-collected T. triangulum for the presence of Trypanosoma, to estimate infectivity., Methods: Horseflies were sampled by the Malaise trap in the forest fragments at the coastal plain and DNA was extracted from whole body flies. The Polymerase Chain Reaction was performed., Results: Horseflies presented amplification of 18S ribosomal gene-specific of Trypanosoma species. DNA sequencing and phylogenetic analysis positioned the strains in the Kaiowa clade with Trypanosoma kaiowa, associated with the crocodilian clade of Trypanosoma., Conclusion: This study represents the first report of the presence of the Tr. kaiowa in T. triangulum and the expansion of the parasite's range further south in South America., (© 2021. Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)

The autonomic nervous system (ANS) and the immune system are deeply interrelated. The ANS regulates both innate and adaptive immunity through the sympathetic and parasympathetic branches, and an imbalance in this system can determine an altered inflammatory response as typically observed in chronic conditions such as systemic autoimmune diseases. Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis all show a dysfunction of the ANS that is mutually related to the increase in inflammation and cardiovascular risk. Moreover, an interaction between ANS and the gut microbiota has direct effects on inflammation homeostasis. Recently vagal stimulation techniques have emerged as an unprecedented possibility to reduce ANS dysfunction, especially in chronic diseases characterized by pain and a decreased quality of life as well as in chronic inflammation.

In the absence of heat stress, females increase blood pressure (BP) during isometric handgrip exercise due to cardiac output more than total peripheral resistance (TPR) compared to men. Although heat stress seems to blunt BP responses at rest and during handgrip, possible sex differences remained unknown. We hypothesized that BP responses during handgrip under a heated environment (HOT) will be different between men and women. Eight healthy men (29 ± 6 years) and eight women (26 ± 4 years) participated in this study. The experimental protocol was separated into two environmental conditions: HOT (~ 36 °C) and thermoneutral (TC; ~ 24 °C). In both conditions, participants rested for 30 min and performed the handgrip for 3 min. BP, heart rate (HR) stroke volume and cardiac output were continuously recorded, and TPR was calculated (TPR = mean blood pressure (MBP)/cardiac output). HOT reduced BP and TPR at baseline and during handgrip in females as compared to TC, while males showed similar responses in both thermal conditions. HR was higher under HOT in both groups. Cardiac output and stroke volume were not different under HOT compared to TC for females. In males, cardiac output increased at the last minute of handgrip under HOT through augmented HR, because stroke volume was unchanged. In conclusion, the main effect of HOT was to shift downwards BP and total peripheral resistance at rest and during isometric exercise in females. In males, the combination of handgrip and HOT increased cardiac output by augmented HR, whereas BP presented similar responses between thermal conditions during handgrip., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Around 27% of South Americans live in central and southern Brazil. Of 19,400 human malaria cases in Brazil in 2018, some were from the southern and southeastern states. High abundance of malaria vectors is generally positively associated with malaria incidence. Expanding geographic distributions of Anopheles vector mosquito species (e.g. A. cruzii) in the face of climate change processes would increase risk of such malaria transmission; such risk is of particular concern in regions that hold human population concentrations near present limits of vector species' geographic distributions. We modeled effects of likely climate changes on the distribution of A. cruzii, evaluating two scenarios of future greenhouse gas emissions for 2050, as simulated in 21 general circulation models and two greenhouse gas scenarios (RCP 4.5 and RCP 8.5) for 2050. We tested 1305 candidate models, and chose among them based on statistical significance, predictive performance, and complexity. The models closely approximated the known geographic distribution of the species under current conditions. Under scenarios of future climate change, we noted increases in suitable area for the mosquito vector species in São Paulo and Rio de Janeiro states, including areas close to 30 densely populated cities. Under RCP 8.5, our models anticipate areal increases of >75% for this important malaria vector in the vicinity of 20 large Brazilian cities. We developed models that anticipate increased suitability for the mosquito species; around 50% of Brazilians reside in these areas, and ∼89% of foreign tourists visit coastal areas in this region. Under climate change thereefore, the risk and vulnerability of human populations to malaria transmission appears bound to increase., (Copyright © 2021. Published by Elsevier B.V.)

Autonomic nervous system (ANS) dysfunction is a well-known feature of cardiovascular diseases (CVDs). Studies on heart rate variability (HRV), a non-invasive method useful in investigating the status of cardiovascular autonomic control, have shown that a predominance of sympathetic modulation not only contributes to the progression of CVDs but has a pivotal role in their onset. Current therapies focus more on inhibition of sympathetic activity, but the presence of drug-resistant conditions and the invasiveness of some surgical procedures are an obstacle to complete therapeutic success. On the other hand, targeting the parasympathetic branch of the autonomic nervous system through invasive vagus nerve stimulation (VNS) has shown interesting results as alternative therapeutic approach for CVDs. However, the invasiveness and cost of the surgical procedure limit the clinical applicability of VNS and hinder the research on the physiological pathway involved. Transcutaneous stimulation of the auricular branch of the vagus nerve (tVNS) seems to represent an important non-invasive alternative with effects comparable to those of VNS with surgical implant. Thus, in the present narrative review, we illustrate the main studies on tVNS performed in healthy subjects and in three key examples of CVDs, namely heart failure, hypertension and atrial fibrillation, highlighting the neuromodulatory effects of this technique., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The current study was undertaken to test the hypothesis that the high physical capacity of rowing athletes may not reverse the influence of age on cardiac autonomic control decline estimated by heart rate variability (HRV). Forty-four male subjects divided in four groups: 11 young athletes (YA; 18 ±1 year), 11 young non-athletes (YNA; 20 ±1 year), 11 middle age athletes (MAA; 43 ±6 years) and 11 middle age non-athletes (MNA; 44 ±8 years) participated in the study. Heart rate (HR) was recorded beat-by-beat for 10 minutes in supine (SUP) and 10 min in orthostatic (ORT) positions. HRV was analyzed in the frequency domain to obtain the spectral power in the high (HF) and low frequency (LF) bands, and the changes to ORT (%∆HRV) were calculated (ORT - SUP / SUP). During SUP, HF was lower in MNA and MA compared to YA and YNA, while LF was lower in MNA than YA. For %ΔHRV, %ΔHF was higher in YA than YNA, MA and MNA. The %ΔLF was not different among groups. In conclusion, aging seems to overcome the influence of physical fitness on neural regulation of the heart, as highlighted by the HRV response to active standing.

Obesity and sleep disturbances are common conditions in modern societies and accumulating evidence support a close bidirectional causal relationship between these two conditions. Indeed, from one side sleep loss seems to affect energy intake and expenditure through its direct effects on hormone-mediated sensations of satiety and hunger and through the influence on hedonic and psychological aspects of food consumption. Sleep deprived patients have been shown to experiment excessive daytime sleepiness, fatigue, and tiredness that, in a vicious circle, enhances physical inactivity and weight gain. On the other side, obesity is a well-known risk factor for several sleep disorders. This narrative review will discuss the main pathophysiological mechanisms that link sleep loss to obesity and metabolic syndrome with particular attention to the three most common sleep disorders (insomnia, obstructive sleep apnoea syndrome, restless leg syndrome)., (Copyright © 2021. Published by Elsevier B.V.)

Objective. To investigate the interplay between active standing and heat stress on cardiovascular autonomic modulation in healthy individuals. Approach. Blood pressure (BP) and ECG were continuously recorded during 30 min in supine (SUP) and 6 min in orthostatic position (ORT) under thermal reference (TC; ∼24 °C) or heated environment (HOT; ∼36 °C) conditions, in a randomized order. All data collection was performed during the winter and spring seasons when typical outdoor temperatures are ∼23 °C. Spectral analysis was employed by the autoregressive model of R-R and systolic blood pressure (SBP) time series and defined, within each band, in low (LF, 0.04 to 0.15 Hz) and high (0.15-0.40 Hz) frequencies. The indices of cardiac sympathetic (LF) and cardiac parasympathetic (HF) were normalized (nu) dividing each band power by the total power subtracted the very-low component (<0.04 Hz), obtaining the cardiac autonomic balance (LF/HF) modulation. The gain of the relationship between SBP and R-R variabilities within the LF band was utilized for analysis of spontaneous baroreflex sensitivity (alpha index; α LF). Nonlinear analysis was employed through symbolic dynamics of R-R, which provided the percentage of sequences of three heart periods without changes in R-R interval (0V%; cardiac sympathetic modulation) and two significant variations (2UV% and 2LV%; cardiac vagal modulation). Main results. HOT increased 0V% and HR, and decreased α LF and 2UV% during SUP compared to TC. During ORT, HOT provokes a greater increment on HR, LF/HF and 0V%, indexes compared to ORT under TC. Significance. At rest, heat stress influences both autonomic branches, increasing sympathetic and decreasing vagal modulation and spontaneous baroreflex sensitivity. The augmented HR during active standing under heat stress seems to be mediated by a greater increment in cardiac sympathetic modulation, showing an interplay between gravitational and thermal stimulus., (© 2021 Institute of Physics and Engineering in Medicine.)

Even though recent studies reported a positive inspiratory muscle training (IMT) effect on cardiovascular autonomic modulation, its underlying mechanisms as the breathing pattern remain unclear. The study aimed to investigate the IMT effects on resting heart rate variability (HRV), spontaneous baroreflex sensitivity (BRS), and spontaneous breathing pattern in older women. Fourteen healthy older women participated in this study, allocated in IMT (50 % MIP; n = 8) or Sham (5% MIP; n = 6) protocols for four weeks. Blood pressure, heart rate, and ventilatory data were continuously recorded before and after interventions. After four weeks, IMT-group increased maximal inspiratory pressure and vagal-mediated HRV, following by the reduction of sympatho-mediated HRV and the inspiratory time during the spontaneous breathing cycle compared to Sham-group, but did not change BRS. Therefore, the shorter inspiratory time suggests a putative mechanism behind improved vagal-mediated HRV post-IMT in older women., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Inspiratory muscle training improved maximal inspiratory pressure (MIP) and vagal-mediated heart rate variability (HRV) in older women. However, it is unknown what occurs if the training is discontinued (detraining protocol). The aim of this study was to investigate the IMT and detraining effects on resting HRV in older women. Twelve healthy older women (60-72 yrs) enrolled in home-based IMT at 50% MIP (IMT-group) or placebo at 5% MIP (Sham-group) protocol for 4 weeks using a mechanical pressure threshold loading device. The participants were not engaged in any other exercise protocol at that time. During IMT and Sham interventions, the inspiratory load was adjusted weekly by the actual MIP and resting heart rate variability (HRV) evaluated. After training cessation (4 weeks of detraining), participants returned to the lab for HRV and MIP recordings. Adherence to IMT was superior to 95%. IMT increased MIP (23 ± 8 cmH 2 O) and vagal-mediated HRV (normalized HF; 37 ± 8%), following by the reduction of sympatho-vagal balance (LF/HF), from the second week to the end of the protocol compared to sham-group. After detraining, IMT-group reduced MIP (-23 ± 8 cmH 2 O) and vagal-mediated HRV (normalized HF; -38 ± 14%) returning to baseline values. In conclusion, MIP and vagal-HRV improvements induced by IMT were reversed by four weeks of detraining., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although cardiac autonomic modulation has been studied in several respiratory diseases, the evidence is limited on lung transplantation, particularly on its acute and chronic effects. Thus, we aimed to evaluate cardiac autonomic modulation before and after bilateral lung transplantation (BLT) through a prospective study on patients enrolled while awaiting transplant., Methods: Twenty-two patients on the waiting list for lung transplantation (11 women, age 33 [24-51] years) were enrolled in a prospective study at Ospedale Maggiore Policlinico Hospital in Milan, Italy. To evaluate cardiac autonomic modulation, ten minutes ECG and respiration were recorded at different time points before (T0) and 15 days (T1) and 6 months (T2) after bilateral lung transplantation. As to the analysis of cardiac autonomic modulation, heart rate variability (HRV) was assessed using spectral and symbolic analysis. Entropy-derived measures were used to evaluate complexity of cardiac autonomic modulation. Comparisons of autonomic indices at different time points were performed., Results: BLT reduced HRV total power, HRV complexity and vagal modulation, while it increased sympathetic modulation in the acute phase (T1) compared to baseline (T0). The HRV alterations remained stable after 6 months (T2)., Conclusion: BLT reduced global variability and complexity of cardiac autonomic modulation in acute phases, and these alterations remain stable after 6 months from surgery. After BLT, a sympathetic predominance and a vagal withdrawal could be a characteristic autonomic pattern in this population.

The aim of this paper is to assess the integrated responses of ambulatory blood pressure (BP), cardiac autonomic modulation, spontaneous baroreflex sensitivity (BRS), and vascular reactivity after a single bout of resistance exercise (RE) in men with stage 2 hypertension who have never been treated before. Ten hypertensive men were subjected to a RE session of three sets of 20 repetitions and an intensity of 40% of the 1-repetition maximum (RM) test in seven different exercises. For the control (CTR) session, the volunteers were positioned on the exercise machines but did not perform any exercise. Forearm blood flow was measured by venous occlusion plethysmography. We also analyzed the heart rate variability (HRV), ambulatory BP, blood pressure variability (BPV), and BRS. All measurements were performed at different timepoints: baseline, 20 min, 80 min, and 24 h after both RE and CTR sessions. There were no differences in ambulatory BP over the 24 h between the RE and CTR sessions. However, the area under the curve of diastolic BP decreased after the RE session. Heart rate (HR) and cardiac output increased for up to 80 and 20 min after RE, respectively. Similarly, forearm blood flow, conductance, and vascular reactivity increased 20 min after RE ( p < 0.05). In contrast, HRV and BRS decreased immediately after exercise and remained lower for 20 min after RE. We conclude that a single bout of RE induced an increase in vascular reactivity and reduced the pressure load by attenuating AUC of DBP in hypertensive individuals who had never been treated with antihypertensive medications., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Marcus Vinicius Machado et al.)

We tested the hypothesis that inspiratory resistive loading (IRL) increases vagal-mediated complexity of heart rate variability (HRV) in older women. We recorded heart rate continually during 30 breaths with Sham or IRL (30 % of maximal inspiratory pressure) in sitting position. The normalized spectral power in the low (LFn) and high (HFn) frequency bands and the symbolic dynamics measures for 0 V, 2UV and 2 L V were obtained. HFn was higher and LFn was lower during IRL than Sham (p < 0.05). During IRL, 2UV component increased more than Sham (p < 0.05) while 0 V index remained unchanged (p> 0.05). In conclusion, acute IRL improved vagal modulation index of both linear (spectral analysis) and non-linear analysis (symbolic dynamics) in older women., (Copyright © 2020 Elsevier B.V. All rights reserved.)